Abstracts

Introduction

Antimicrobial medicines now save millions of lives each year and many infectious diseases are far less deadly because of them.¹1. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013 Dec;13(12):1057-98.http://dx.doi.org/10.1016/S1473-3099(13)70318-9PMID:24252483
http://dx.doi.org/10.1016/S1473-3099(13)... However, bacteria, viruses, parasites and fungi develop resistance to existing medicines and few novel antimicrobial products are being produced. Antimicrobial resistance - i.e. resistance of microorganisms to an antimicrobial drug that was originally effective for treating the infection it causes - is both natural and inevitable. However, inappropriate antimicrobial use, falsified or substandard drugs and poor infection control accelerate the pace of evolutionary processes.¹1. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013 Dec;13(12):1057-98.http://dx.doi.org/10.1016/S1473-3099(13)70318-9PMID:24252483
http://dx.doi.org/10.1016/S1473-3099(13)...

Today, diminishing antimicrobial effectiveness represents one of the greatest threats to human health.²2. Global risks 2013 report. 8th ed. Geneva: World Economic Forum; 2013. Available from: http://www3.weforum.org/docs/WEF_GlobalRisks_Report_2013.pdf
http://www3.weforum.org/docs/WEF_GlobalR...

3. Jonathan HGE, Stoltenberg RHJ. UN commission on life-saving commodities for women and children. New York: United Nations; 2012. Available from: Available from: http://unfpa.org/webdav/site/global/shared/images/publications/2012/Final%20UN%20Commission%20Report_14sept2012.doc [cited 2014 Jul 17].
http://unfpa.org/webdav/site/global/shar... ^-44. Davies SC, Fowler T, Watson J, Livermore DM, Walker D. Annual report of the Chief Medical Officer: infection and the rise of antimicrobial resistance. Lancet. 2013 May 11;381(9878):1606-9. http://dx.doi.org/10.1016/S0140-6736(13)60604-2PMID:23489756
http://dx.doi.org/10.1016/S0140-6736(13)... Annual deaths from drug-resistant infection are projected to increase from 700 000 to 10 million by 2050, at a cumulative cost of 100 trillion United States dollars (US$).⁴4. Davies SC, Fowler T, Watson J, Livermore DM, Walker D. Annual report of the Chief Medical Officer: infection and the rise of antimicrobial resistance. Lancet. 2013 May 11;381(9878):1606-9. http://dx.doi.org/10.1016/S0140-6736(13)60604-2PMID:23489756
http://dx.doi.org/10.1016/S0140-6736(13)... ^,55. Review on Antimicrobial Resistance. Tackling drug-resistant infections globally [Internet]. London: Wellcome Trust; 2014. Available from:http://amr-review.org
http://amr-review.org... The world might face a scenario where infection once again takes a heavy toll on a scale and severity not seen in over 80 years. Universal access to antimicrobials, on the other hand, represents one of the greatest opportunities to save millions of lives each year and improve the lives of millions more. For example, 244 000 deaths in neonates could be averted annually with basic injectable antibiotics.³3. Jonathan HGE, Stoltenberg RHJ. UN commission on life-saving commodities for women and children. New York: United Nations; 2012. Available from: Available from: http://unfpa.org/webdav/site/global/shared/images/publications/2012/Final%20UN%20Commission%20Report_14sept2012.doc [cited 2014 Jul 17].
http://unfpa.org/webdav/site/global/shar...

Global action is needed to mitigate the threat of increased antimicrobial resistance. However, policies designed to improve access to antimicrobial medicines, to maintain their effectiveness and to increase the supply of new products have not been implemented.¹1. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013 Dec;13(12):1057-98.http://dx.doi.org/10.1016/S1473-3099(13)70318-9PMID:24252483
http://dx.doi.org/10.1016/S1473-3099(13)... We argue that this lack of action is due to failures in global governance and global markets, rather than insufficient awareness or political priority. National governments would all benefit from cooperation and coordination on antimicrobial access, conservation and innovation, but none want to incur their part of the associated costs.⁶6. Fidler DP. Legal issues associated with antimicrobial drug resistance. Emerg Infect Dis. 1998 Apr-Jun;4(2):169-77. http://dx.doi.org/10.3201/eid0402.980204PMID:9621187
http://dx.doi.org/10.3201/eid0402.980204... ^,77. Smith RD, Coast J. Antimicrobial resistance: a global response. Bull World Health Organ. 2002;80(2):126-33. PMID:11953791 Global markets, meanwhile, undersupply antimicrobials for those who cannot afford them, oversupply them in wealthier contexts where individual benefits are not weighed against total costs and underinvest in research and development for new antimicrobials.⁸8. Outterson K. New business models for sustainable antibiotics. London: Chatham House; 2014. p. 31. Available from: Available from: http://www.chathamhouse.org/sites/files/chathamhouse/public/Research/Global%20Health/0214SustainableAntibiotics.pdf [cited 2014 Apr 22].
http://www.chathamhouse.org/sites/files/...

We examine ways of achieving global collective action to correct these governance and market failures. Overcoming these failures should make it possible to implement policies designed to improve access to antimicrobials, conserve those that are still effective and drive innovation in preventing and treating infections. We map the existing actors in this policy area, identify guiding institutional design principles and evaluate 10 options for achieving progress. Our goal is to bring the science of global strategy⁹9. Hoffman SJ. A Science of Global Strategy. In: Frenk J, Hoffman SJ, editors. "To save humanity": what matters most for a healthy future. Oxford: Oxford University Press; 2015. to bear on the challenge of antimicrobial resistance.

Governance of antimicrobial use

Many institutions address the threat posed by antimicrobial resistance (Box 1), with numerous global strategies, political resolutions and regulatory standards generated from multilateral activities, industry initiatives and public-private partnerships. However, the mandates and objectives of these institutions are not all aligned. For example, antimicrobial growth-promoters can advance Food and Agriculture Organization (FAO) objectives by improving weight gain in farm animals, but can adversely affect human health, of concern for the World Health Organization (WHO). These institutions work through different policy fora which have different powers to influence state behaviour and are attended by different delegations with different priorities. Ministers of agriculture attend FAO meetings, while ministers of health are at WHO. There is no forum in which they meet to resolve issues of common concern - such as antimicrobial resistance - on the international level. Commitments made by ministers of health to address the issue have resulted in several World Health Assembly resolutions (e.g. WHA51.17, WHA54.11, WHA54.14 and WHA58.27) that have not been implemented. In 2007, WHO reported that:

Nonetheless, some progress towards global collective action on antimicrobials has been made in recent years, in areas such as disease surveillance and food safety. Numerous pathogen- and region-specific surveillance networks are supported by WHO. The International Health Regulations require that all WHO Member States monitor and report disease outbreaks. The World Organization for Animal Health (OIE) sets global standards for antimicrobial surveillance programmes.¹¹11. Terrestrial animal health code [Internet]. Paris: World Organisation for Animal Health; 2013. Available from: Available from: http://www.oie.int/international-standard-setting/terrestrial-code/ [cited 2014 Jul 16].
http://www.oie.int/international-standar... FAO, WHO and OIE are currently developing an agreed strategy on antimicrobial resistance.¹²12. The FAO-OIE-WHO Collaboration: Sharing responsibilities and coordinating global activities to address health risks at the animal-human-ecosystems interface. Paris: World Organisation for Animal Health ; 2010. Available from: Available from: http://www.oie.int/fileadmin/home/eng/current_scientific_issues/docs/pdf/final_concept_note_hanoi.pdf [cited 2015 Sep 25].
http://www.oie.int/fileadmin/home/eng/cu... ^,1313. Otto P. FAO-OIE-WHO tripartite positions and actions on antimicrobial resistance. Rome: Food and Agriculture Organization; 2013. Available from: Available from: http://www.rr-africa.oie.int/docspdf/en/2013/VP/12.OTTO.pdf [cited 2015 Sep 25].
http://www.rr-africa.oie.int/docspdf/en/... FAO and WHO already cooperate in the Codex Alimentarius Commission, which develops harmonized international food standards that protect consumer health.¹⁴14. Codex Alimentarius Commission. Guidelines for risk analysis of foodborne antimicrobial resistance. Geneva: Food and Agriculture Organization; 2011. Available from: Available from: http://www.codexalimentarius.net/input/download/standards/11776/CXG_077e.pdf [cited 2015 Sep 25].
http://www.codexalimentarius.net/input/d...

However, it is not clear that the promise of these collaborative efforts will be realized. Debates between human and animal health researchers over drivers of antimicrobial resistance have hindered joint efforts;¹⁵15. Strategic and Technical Advisory Group on Antimicrobial Resistance: report of the first meeting. Geneva: World Health Organization ; 2013. Available from: Available from: http://www.who.int/drugresistance/stag/amr_stag_meetingreport0913.pdf [cited 2015 Sep 25].
http://www.who.int/drugresistance/stag/a... the global antimicrobial regime lacks clear leadership and remains fragmented.¹⁶16. Transatlantic Taskforce on Antimicrobial Resistance. Recommendations for future collaboration between the US and EU. Stockholm: European Centre for Disease Prevention and Control; 2011. p. 44. Real-world achievements have been elusive. Of the 152 OIE Member States that responded to a 2012 survey, only 27% had systems for monitoring antimicrobial usage in animals, as prescribed by theTerrestrial Animal Health Code , with implementation lowest in Africa (5%) and the Americas (4%).¹⁷17. Diaz F. Collection of quantitative data on the use of antimicrobial agents. Paris: World Organisation for Animal Health ; 2013. Available from: Available from: http://www.rr-africa.oie.int/docspdf/en/2013/VP/13.DIAZ.pdf [cited 2015 Sep 25].
http://www.rr-africa.oie.int/docspdf/en/... A recent systematic review found that use of human antimicrobial medicines without prescription in countries outside northern Europe and North America ranged from 19% to 100%.¹⁸18. Morgan DJ, Okeke IN, Laxminarayan R, Perencevich EN, Weisenberg S. Non-prescription antimicrobial use worldwide: a systematic review. Lancet Infect Dis . 2011 Sep;11(9):692-701. http://dx.doi.org/10.1016/S1473-3099(11)70054-8PMID:21659004
http://dx.doi.org/10.1016/S1473-3099(11)... The International Health Regulations have potential to improve this situation, but in 2014, 81 Member States requested a second two-year extension to their original June 2012 deadline for attaining minimal core public health capacities. An additional 48 Member States did not communicate their implementation status or intentions.¹⁹19. Ijaz K, Kasowski E, Arthur RR, Angulo FJ, Dowell SF. International Health Regulations - what gets measured gets done. Emerg Infect Dis . 2012 Jul;18(7):1054-7. http://dx.doi.org/10.3201/eid1807.120487PMID:22709593
http://dx.doi.org/10.3201/eid1807.120487...

20. Edge JS, Hoffman SJ. Strengthening national health systems' capacity to respond to future global pandemics. In: Davies S, Youde JR, editors. The politics of surveillance and responses to disease outbreaks. Surrey: Ashgate Publishing; 2015. pp. 157-79.^-2121. Implementation of the International Health Regulations (2005): report by the Director-General. Geneva: World Health Organization ; 2015. Available from: http://apps.who.int/gb/ebwha/pdf_files/WHA66/A66_16-en.pdf
http://apps.who.int/gb/ebwha/pdf_files/W... The World Health Assembly approved aGlobal Action Plan on Antimicrobial Resistance in May 2015, but its full implementation has yet to be funded and is far from guaranteed.²²22. Draft global action plan on antimicrobial resistance. Geneva: World Health Organization ; 2014. Available from: Available from: http://apps.who.int/gb/ebwha/pdf_files/EB136/B136_20-en.pdf [cited 2015 Oct 9].
http://apps.who.int/gb/ebwha/pdf_files/E...

Four institutional weaknesses contribute to the global lack of action on antimicrobial resistance. The first is a governance problem - an absence of effective coordination across the actors working in different sectors to address this challenge. The second is a compliance problem - a gap between the many actions that have been promised by states and the few that have been delivered. The third is a leadership problem - insufficient political will to stop the inappropriate use of antimicrobials in humans and animals. The fourth is a financing problem - insufficient resources to implement antimicrobial policies.

In the absence of consent-based global action, governments may resort to unilateral measures to coerce collective action, such as direct financing, conditionality, import and export bans or sanctions. These approaches may work but they have several disadvantages (Table 1).

Strengthening institutions

To correct governance gaps and market failures, the global antimicrobial regime can be changed by adding to or reforming three sets of institutional mechanisms: (i) decision-making mechanisms for setting norms, soliciting advice, making decisions, appealing decisions and resolving disputes; (ii) operational mechanisms for administering activities, for raising, managing and spending funds and for financial auditing; and (iii) accountability mechanisms for making commitments, encouraging compliance, promoting transparency, ensuring oversight and learning from experience.²³23. Hoffman SJ, Røttingen J-A. Assessing implementation mechanisms for an international agreement on research and development for health products. Bull World Health Organ . 2012 Nov 1;90(11):854-63. http://dx.doi.org/10.2471/BLT.12.109827PMID:23226898
http://dx.doi.org/10.2471/BLT.12.109827...

The optimal package of institutional mechanisms would address current weaknesses by offering effective governance, universal compliance, competent leadership and sufficient financing. Past experience and knowledge of international relations, law and political science offer at least six institutional design principles that can guide us.

First, global institutions are well positioned to serve some functions and not others because governments commit to and comply with international rules for particular reasons. For example, realist scholars argue international relations primarily reflect states' own rational self-interests and pursuit of wealth, power and status.²⁴24. Baldwin DA, editor. Neorealism and neoliberalism: the contemporary debate. New York: Columbia University Press; 1993.Institutionalists believe states cooperate and coordinate to maximize utility under conditions of interdependence.²⁵25. Keohane RO. Institutionalist theory and the realist challenge after the cold war. Boston: Center for International Affairs, Harvard University; 1993. pp 54. Liberal theorists suggest that domestic ideas, interests and institutions affect states' international relations by shaping state preferences.²⁶26. Simmons BA. Mobilizing for human rights: international law in domestic politics. Cambridge: Cambridge University Press; 2009. pp. 451.http://dx.doi.org/10.1017/CBO9780511811340
http://dx.doi.org/10.1017/CBO97805118113... Constructivists argue that state behaviour is shaped by ideas, including those derived from international engagement.²⁷27. Finnemore M. National interests in international society. Ithaca, NY: Cornell University Press; 1996. pp. 180. While these theories sometimes conflict, together they suggest global institutions should advance states' rational self-interests, address cooperation and coordination problems, empower domestic actors or change ideas about the world. The impact of any function that global institutions serve also depends critically on states perceiving the function to be a legitimate exercise of delegated authority,²⁸28. Franck TM. The power of legitimacy among nations. Oxford: Oxford University Press ; 1990. pp. 318. having sufficient capacity to change²⁹29. Chayes A, Chayes AH. The new sovereignty: compliance with international regulatory agreements. Cambridge, MA: Harvard University Press; 1996. pp. 432. and being able to internalize international norms into domestic processes.³⁰30. Koh HH. Why do nations obey international law? Yale Law Journal. 1997;106:2599-659. http://dx.doi.org/10.2307/797228
http://dx.doi.org/10.2307/797228...

Second, global institutions addressing antimicrobial access, conservation and innovation should have clear mandates to ensure they maximize benefits, minimize costs, manage risks and balance trade-offs. International activities are not without costs or risks of harm. There are direct costs like staff salaries, meetings, travel, communications, governance structures and management, and indirect opportunity costs and potential risks of paternalism in placing international norms above local priorities.³¹31. Hoffman SJ, Røttingen J-A. A framework convention on obesity control? Lancet. 2011 Dec 17;378(9809):2068. http://dx.doi.org/10.1016/S0140-6736(11)61894-1PMID:22177507
http://dx.doi.org/10.1016/S0140-6736(11)... Global institutions thus need to be cognizant of these costs and risks, maximize existing institutional architecture and work with others to minimize destructive competition and inefficient duplication.

Third, the forum through which global institutions are created or reformed is important. Different fora have different members, mandates and powers that place structural limits on their activities and competence. The choice of forum for international action also matters because different communities and groups work through different international fora.³²32. Slaughter A-M. A new world order. Princeton: Princeton University Press; 2005. Available from: Available from: http://site.ebrary.com/id/10312479 [cited 2014 Jul 16].
http://site.ebrary.com/id/10312479... For example, since the Framework Convention on Tobacco Control was negotiated through WHO, the influence of health authorities was amplified and the tobacco industry was marginalized. The United Nations (UN) General Assembly, alternatively, has facilitated higher-level whole-of-government engagement with the issues raised by human immunodeficiency virus (HIV), noncommunicable diseases (NCDs) and universal health coverage in a way that seems particularly useful for intersectoral challenges.³³33. Declaration of commitment on HIV/AIDS: United Nations General Assembly special session on HIV/AIDS. New York: United Nations ; 2001. p. 47. Available from: Available from: http://data.unaids.org/publications/irc-pub03/aidsdeclaration_en.pdf [cited 2014 Jul 10]
http://data.unaids.org/publications/irc-... ^,3434. Global health and foreign policy A/67/L.36. In: Sixty-seveth session United Nations General Assembly, Agenda item 123 [Internet] . New York: United Nations ; 6 December 2012. p. 6. Available from: Available from: http://www.un.org/ga/search/view_doc.asp?symbol=A/67/L.36 [cited 2015 Sep 25].
http://www.un.org/ga/search/view_doc.asp... However, even the most theoretically well-suited fora may sometimes need to be bypassed if they are too slow, inefficient or otherwise ineffective.³⁵35. Prado MM. Institutional bypass: an alternative for development reform [Internet]. Rochester: Social Science Research Network; 2011. Available from: Available from: http://papers.ssrn.com/abstract=1815442 [cited 2014 Jul 22].
http://papers.ssrn.com/abstract=1815442... ^,3636. Hoffman SJ, Røttingen J-A. Split WHO in two: strengthening political decision-making and securing independent scientific advice. Public Health. 2014 Feb;128(2):188-94. http://dx.doi.org/10.1016/j.puhe.2013.08.021PMID:24434035
http://dx.doi.org/10.1016/j.puhe.2013.08...

Fourth, global institutions must be specifically tailored for the nature of the problems they are created or reformed to solve. Many global institutions are state-centric which means that they primarily involve national governments and depend on them to regulate nongovernmental actors within their territories. More meaningful involvement of civil society, industry and health-care organizations may strengthen functions that depend on them. Although in this case, reliance on coercive regulation - such as restricting access to antimicrobials - means that states must take centre stage.³⁷37. Hoffman SJ. The evolution, etiology and eventualities of the global health security regime. Health Policy Plan. 2010 Nov;25(6):510-22.http://dx.doi.org/10.1093/heapol/czq037 PMID:20732860
http://dx.doi.org/10.1093/heapol/czq037...

Fifth, there seems to be an inverse relationship between the strength of international commitment mechanisms and the activities, norms or standards they involve.³⁸38. Hoffman SJ, Røttingen J-A, Frenk J. Assessing proposals for new global health treaties: an analytic framework. Am J Public Health. 2015 Aug;105(8):1523-30. http://dx.doi.org/10.2105/AJPH.2015.302726PMID:26066926
http://dx.doi.org/10.2105/AJPH.2015.3027... This is because agreements are negotiated as a whole, explaining why states regularly adopt treaties - the strongest international commitment mechanism available - then empty them of ambitious content, which they instead reserve for non-binding commitment mechanisms like political declarations and unilateral statements.³⁸38. Hoffman SJ, Røttingen J-A, Frenk J. Assessing proposals for new global health treaties: an analytic framework. Am J Public Health. 2015 Aug;105(8):1523-30. http://dx.doi.org/10.2105/AJPH.2015.302726PMID:26066926
http://dx.doi.org/10.2105/AJPH.2015.3027... For example, regimes governing trade, human rights, disarmament, prisoners of war and money laundering generally rely on different enforcement mechanisms based on the type of problems addressed and the commitments states are willing to undertake (Box 2).³⁹39. Hoffman SJ, Ottersen T. Addressing antibiotic resistance requires robust international accountability mechanisms. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:53-64. PMID:26243244 There is no general hierarchy of impact or influence among global institutions. To strengthen global collective action on antimicrobials, the functions sought, the form that follows and the forum of implementation need to be carefully matched.⁴⁰40. Rizvi Z, Hoffman SJ. Effective global action on antibiotic resistance requires careful consideration of convening fora. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:74-8. PMID:26243247

Sixth, global institutions should be designed for political robustness to withstand inequalities in decision-making and diplomacy.⁴¹41. Hoffman SJ. Mitigating inequalities of influence among states in global decision making. Glob Policy. 2012 Nov;3(4):421-32. http://dx.doi.org/10.1111/j.1758-5899.2011.00153.x
http://dx.doi.org/10.1111/j.1758-5899.20... A realistic view is needed on what different actors can and will do both domestically and internationally, whether by choice or limited by domestic regulations, resources and political constraints. This also means supporting institutions that help enact policy, incentives for those with power to act upon them and interest mobilizers to make the case for their implementation.⁴²42. Hoffman SJ, Røttingen J-A. Assessing the expected impact of global health treaties: evidence from 90 quantitative evaluations. Am J Public Health. 2015 Jan;105(1):26-40. http://dx.doi.org/10.2105/AJPH.2014.302085PMID:25393196
http://dx.doi.org/10.2105/AJPH.2014.3020...

Ten policy options

There are many options for global collective action on antimicrobial medicines, ranging from setting implementation milestones,¹1. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013 Dec;13(12):1057-98.http://dx.doi.org/10.1016/S1473-3099(13)70318-9PMID:24252483
http://dx.doi.org/10.1016/S1473-3099(13)... to providing new financial models,⁴³43. Brogan DM, Mossialos E. Incentives for new antibiotics: the options market for antibiotics (OMA) model. Global Health. 2013;9(1):58.http://dx.doi.org/10.1186/1744-8603-9-58PMID:24199835
http://dx.doi.org/10.1186/1744-8603-9-58... ^,4444. Hollis A, Ahmed Z. Preserving antibiotics, rationally. N Engl J Med. 2013 Dec 26;369(26):2474-6. http://dx.doi.org/10.1056/NEJMp1311479PMID:24369073
http://dx.doi.org/10.1056/NEJMp1311479... to creating new structures,⁴⁵45. Woolhouse M, Farrar J. Policy: an intergovernmental panel on antimicrobial resistance. Nature. 2014 May 29;509(7502):555-7. http://dx.doi.org/10.1038/509555a PMID:24877180
http://dx.doi.org/10.1038/509555a... to adopting legally-binding treaties.⁷7. Smith RD, Coast J. Antimicrobial resistance: a global response. Bull World Health Organ. 2002;80(2):126-33. PMID:11953791^,4646. Hoffman SJ, Outterson K, Røttingen J-A, Cars O, Clift C, Rizvi Z, et al. An international legal framework to address antimicrobial resistance. Bull World Health Organ . 2015 Feb 1;93(2):66. http://dx.doi.org/10.2471/BLT.15.152710PMID:25883395
http://dx.doi.org/10.2471/BLT.15.152710... ^,4747. Behdinan A, Hoffman SJ, Pearcey M. Some global policies for antibiotic resistance depend on legally binding and enforceable commitments. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:68-73. PMID:26243246We present 10 options for achieving global collective action that illustrate the range of what is possible. Each is assessed according to the global institutional weaknesses addressed and the antimicrobial policy imperatives served (Table 2).

Options one to four primarily involve building institutions, ranging in formality. The first is for a global governing body to create milestones and indicators that would then be annually monitored.¹1. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013 Dec;13(12):1057-98.http://dx.doi.org/10.1016/S1473-3099(13)70318-9PMID:24252483
http://dx.doi.org/10.1016/S1473-3099(13)... Like the Millennium Development Goals, milestones can serve as a commitment device and help promote action if actors know they will be regularly assessed, praised for progress and shamed for any lapses. The second option is a code of practice that outlines minimum expectations for willing signatories. Like the Monterrey Consensus on development assistance targets and the WHO Code of Practice on the International Recruitment of Health Personnel, norms can promote compliance through informal governmental networks and the desire to avoid being seen as "bad". The third option is a UN inter-agency task force that coordinates the activities of the many UN entities working in this policy area and provides clear direction and leadership for stakeholders. Such task forces exist for NCDs, disaster reduction and violence against women. The fourth option is an intergovernmental panel - like the UN Intergovernmental Panel on Climate Change - that marshals available evidence to inform policies on global antimicrobial resistance.⁴⁵45. Woolhouse M, Farrar J. Policy: an intergovernmental panel on antimicrobial resistance. Nature. 2014 May 29;509(7502):555-7. http://dx.doi.org/10.1038/509555a PMID:24877180
http://dx.doi.org/10.1038/509555a... ^,4848. Sandberg K, Hoffman SJ, Pearcey M. Lessons for global health from global environmental governance. London: Chatham House ; 2015. Available from: Available from: http://www.chathamhouse.org/sites/files/chathamhouse/field/field_document/20150119GlobalHealthEnvironmentSandbergHoffmanPearcey.pdf [cited 2014 Jul 16].
http://www.chathamhouse.org/sites/files/...

Options five to seven primarily involve crafting incentives. Option five is a funding agreement between development agencies and institutions that can promote antimicrobial access, conservation and/or innovation. Option six is a global pooled fund that allocates contributions from various donors to finance policies, reward milestones achieved or provide incentives for research and development. Option seven is for multilateral organizations to impose conditions on any support that they provide, such as requiring governments to share surveillance data or ensure that their citizens have access to antimicrobial medicines before receiving additional aid, gaining trade advantages or participating in international initiatives.

Options eight to 10 primarily involve mobilizing interests at a range of scales. Option eight is to appoint a special representative, like the UN Human Rights Council's special rapporteurs or the UN Secretary-General's envoys, who would use the prestige of their office to rally interest groups, coordinate advocacy, attract attention and encourage action. Option nine is to appoint a high-level panel of eminent persons that would use their access to people in power to apply political pressure. Option 10 is a multi-stakeholder partnership, like the UN Secretary-General's Every Woman Every Child movement, which involves an alliance of many actors, working groups and advocacy across fora.

While each option has its merits, none is individually sufficient. Instead, multiple options will need to be adopted - with global decision-makers able to mix-and-match, hopefully in a way that builds on comparative advantages. As a starting point, the optimal package of options probably includes at least one from each of the three categories: institutions, incentives and interest mobilizers.⁴²42. Hoffman SJ, Røttingen J-A. Assessing the expected impact of global health treaties: evidence from 90 quantitative evaluations. Am J Public Health. 2015 Jan;105(1):26-40. http://dx.doi.org/10.2105/AJPH.2014.302085PMID:25393196
http://dx.doi.org/10.2105/AJPH.2014.3020... Within the institutional options, monitored milestones and an inter-agency task force seem most promising, especially given the failure of previous codes of practice,⁴⁹49. Edge JS, Hoffman SJ. Empirical impact evaluation of the WHO global code of practice on the international recruitment of health personnel in Australia, Canada, UK and USA. Global Health. 2013;9(1):60. http://dx.doi.org/10.1186/1744-8603-9-60PMID:24228827
http://dx.doi.org/10.1186/1744-8603-9-60... including those involving antimicrobial medicines.¹⁷17. Diaz F. Collection of quantitative data on the use of antimicrobial agents. Paris: World Organisation for Animal Health ; 2013. Available from: Available from: http://www.rr-africa.oie.int/docspdf/en/2013/VP/13.DIAZ.pdf [cited 2015 Sep 25].
http://www.rr-africa.oie.int/docspdf/en/... ^,5050. Bruno AV, Mackay C. Antimicrobial resistance and the activities of the Codex Alimentarius Commission. Rev Sci Tech. 2012 Apr;31(1):317-23. PMID:22849286 Existing mechanisms to achieve scientific consensus in medicine and public health probably make a big intergovernmental panel unnecessary.⁴⁸48. Sandberg K, Hoffman SJ, Pearcey M. Lessons for global health from global environmental governance. London: Chatham House ; 2015. Available from: Available from: http://www.chathamhouse.org/sites/files/chathamhouse/field/field_document/20150119GlobalHealthEnvironmentSandbergHoffmanPearcey.pdf [cited 2014 Jul 16].
http://www.chathamhouse.org/sites/files/... For incentives, a global pooled fund seems to dominate the other options. Funding agreements address few of the political economy challenges faced and it could be unethical to put conditions on support given to states. Appointing a special representative seems the most practical option for mobilizing interests. A special representative could achieve similar outcomes to a far costlier high-level panel and is more feasible than a multi-stakeholder partnership.

An international legal framework

In addition to options for building institutions, crafting incentives and mobilizing interests, an international legal framework for antimicrobial resistance could be used to combine different options.⁴⁶46. Hoffman SJ, Outterson K, Røttingen J-A, Cars O, Clift C, Rizvi Z, et al. An international legal framework to address antimicrobial resistance. Bull World Health Organ . 2015 Feb 1;93(2):66. http://dx.doi.org/10.2471/BLT.15.152710PMID:25883395
http://dx.doi.org/10.2471/BLT.15.152710... Of the many global health challenges for which treaties have been proposed, the problem of antimicrobial resistance is a strong candidate for an international treaty.³⁸38. Hoffman SJ, Røttingen J-A, Frenk J. Assessing proposals for new global health treaties: an analytic framework. Am J Public Health. 2015 Aug;105(8):1523-30. http://dx.doi.org/10.2105/AJPH.2015.302726PMID:26066926
http://dx.doi.org/10.2105/AJPH.2015.3027... ^,5151. Hoffman SJ, Røttingen JA, Frenk J. International law has a role to play in addressing antibiotic resistance. J Law Med Ethics . 2015 Jun;43(2) Suppl 3:65-7. PMID:26243245

Support for an international legal framework is justified given that antimicrobial resistance is a major transnational risk involving the global exploitation of an essential common resource for which legal instruments have a reasonable chance of achieving benefits and alternative commitment mechanisms have thus far proven ineffective.³⁸38. Hoffman SJ, Røttingen J-A, Frenk J. Assessing proposals for new global health treaties: an analytic framework. Am J Public Health. 2015 Aug;105(8):1523-30. http://dx.doi.org/10.2105/AJPH.2015.302726PMID:26066926
http://dx.doi.org/10.2105/AJPH.2015.3027... ^,5151. Hoffman SJ, Røttingen JA, Frenk J. International law has a role to play in addressing antibiotic resistance. J Law Med Ethics . 2015 Jun;43(2) Suppl 3:65-7. PMID:26243245 Like the legs of a tripod, each antimicrobial policy imperative - access, conservation and innovation - requires a strong, simultaneous level of support from the other two. This is because the policy imperatives are mutually reinforcing: untreated infections spread resistance and the size of market is smaller when many people have no access to antimicrobials; resistance diminishes the value of access to existing antimicrobials and puts a time-limit on their sale; and innovation needs both appropriate access and conservation policies to ensure there can be a return on investment.⁴⁶46. Hoffman SJ, Outterson K, Røttingen J-A, Cars O, Clift C, Rizvi Z, et al. An international legal framework to address antimicrobial resistance. Bull World Health Organ . 2015 Feb 1;93(2):66. http://dx.doi.org/10.2471/BLT.15.152710PMID:25883395
http://dx.doi.org/10.2471/BLT.15.152710... An international legal framework may be the best way to achieve progress on all three components at once.⁴⁷47. Behdinan A, Hoffman SJ, Pearcey M. Some global policies for antibiotic resistance depend on legally binding and enforceable commitments. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:68-73. PMID:26243246

Fora for implementation

If decision-makers take action, they must decide whether to reform existing global institutions or to create something new. From a policy perspective, it is appealing to create stand-alone initiatives either under sponsorship of an existing organization or through a new forum. WHO is the most obvious existing organization, especially given its unusually expansive powers for making new international treaties under Articles 19 and 21 of its Constitution. Yet WHO's current financing and governance challenges indicate that an alternative forum may be needed.³⁶36. Hoffman SJ, Røttingen J-A. Split WHO in two: strengthening political decision-making and securing independent scientific advice. Public Health. 2014 Feb;128(2):188-94. http://dx.doi.org/10.1016/j.puhe.2013.08.021PMID:24434035
http://dx.doi.org/10.1016/j.puhe.2013.08... ^,5252. Clift C. What's the World Health Organization for? London: Chatham House ; 2014. Available from: Available from: http://observgo.uquebec.ca/observgo/fichiers/88303_20140521WHOHealthGovernanceClift.pdf [cited 2014 Jul 9].
http://observgo.uquebec.ca/observgo/fich... Alternatives include bodies like FAO, OIE, the UN General Assembly and UN Security Council, or smaller groupings like the G7/G8, G20, G77, or the Oslo-7 Foreign Policy and Global Health countries.⁴⁰40. Rizvi Z, Hoffman SJ. Effective global action on antibiotic resistance requires careful consideration of convening fora. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:74-8. PMID:26243247 Other platforms, like the UN Office for Disarmament Affairs and the Biological Weapons Convention, could also be relevant for specific functions such as antimicrobial surveillance as they have become increasingly important fora for addressing infectious disease threats.

From a political economy perspective, stand-alone initiatives may not be possible. Institutions, incentives and interests may not coalesce into a workable package of policy prescriptions and implementation mechanisms. The momentum generated by existing institutions, incentives in other policy areas and interest mobilizers may need to be harnessed. Incorporating policies and mechanisms into existing platforms may help overcome the high threshold for starting something new while simultaneously facilitating cross-forum bargaining. Such incorporation will influence the final policies adopted, depending on how decisions are made, who is involved, which actors dominate, where priorities lie, and pre-existing informal bargains. Rules made through sector-based fora will naturally favour the relevant sector.⁴⁰40. Rizvi Z, Hoffman SJ. Effective global action on antibiotic resistance requires careful consideration of convening fora. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:74-8. PMID:26243247

Conclusion

Despite considerable challenges and a history of inaction on antimicrobial resistance, progress should be possible if policy options are matched with the right forum that aligns institutions, incentives and interests towards global collective action. What is needed is a commitment to action and implementation of the many recommendations that have already been made, especially WHO's Global Action Plan on Antimicrobial Resistance .²²22. Draft global action plan on antimicrobial resistance. Geneva: World Health Organization ; 2014. Available from: Available from: http://apps.who.int/gb/ebwha/pdf_files/EB136/B136_20-en.pdf [cited 2015 Oct 9].
http://apps.who.int/gb/ebwha/pdf_files/E... Global decision-makers must now combine the science of strategy with the art of the possible. Preserving and continuing advances in global health depend on doing so.

Acknowledgements

We thank participants of seminars at Chatham House in London, England, the Dag Hammarskjöld Foundation in Uppsala, Sweden, and the International Studies Association Conference 2014 in Toronto, Canada.

References

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History